Fibronectin is a large multidomain protein with numerous functions. The tenth module contains the RGD cell attachment sequence while the ninth module contains the synergy region. The domain consisting of the ninth and tenth type III modules has full fibronectin binding activity to the specific integrin receptor, alpha5-beta1. We have recently attained our goal of determining the three dimensional structure of this two-module domain. Although the structures of the individual modules generally agree with the recently published crystal structure of the human fibronectin 7-10 fragment, there are clear and important differences between the solution and crystals structures. For example the RGD cell binding loop is well ordered in the crystal structure but is highly flexible in solution. Furthermore the 9th and 10th modules form a highly extended and well ordered structure in the crystal, whereas the available NMR data in solution agrees that the two modules form an extended structure, but one that allows significant flexibility in the relative orientation of the two modules. Hence, the RGD and SYNERGY regions are not rigidly positioned in the solution structures. We suggest that relative location of the RGD and SYNERGY regions are reasonably well defined in the cell attachment domain, and this is the source of binding specificity. On the other hand, our work suggests that the cell attachment domain possesses sufficient flexibility to permit it to interact with integrins of varying structures.